Nuclear singlet states as a contrast mechanism for NMR spectroscopy

#The invention relates generally to the field Nuclear Magnetic Resonance (NMR). In particular, the invention relates to techniques utilizing nuclear spin singlet states, e.g., for creating contrast enhancement in NMR spectroscopy.

#Nuclear magnetic resonance (NMR) spectroscopy provides a quantitative, non-destructive measure of chemical concentrations in complex mixtures both in vitro and in vivo. In many samples, the spectral lines are narrow while the range of resonance frequencies is broad, and there is little overlap of spectral lines.

#Nuclear magnetic resonance spectra of complex chemical mixtures often contain, however, unresolved and unseen spectral components, especially when a strong background spectrum overlaps weaker peaks. For example, mixtures of biomolecules, such as blood, urine, and brain tissue, often contain a large number of compounds with spectral lines mostly overlapped by a few dominant metabolites. Furthermore, some abundant metabolites, such as glutamine and glutamate, have such similar structures that their spectra are nearly identical and are difficult to resolve from one another. In all these cases, no amount of signal averaging can improve the resolution.

#FIG. 1A illustrates a basic SUCCESS pulse sequence; FIG. 1B illustrates an optimized SUCCESS pulse sequence; FIG. 1C illustrates a simulated NMR signal intensity map for N-acetylaspartic acid; and FIG. 1D illustrates a simulated NMR signal intensity map for aspartic acid.

#FIGS. 2A-2F illustrate measured NMR spectra for one-pulse (left column) and SUCCESS (right column) experiments performed on solutions of N-acetylaspartate (NAA), aspartate (Asp), and their mixture (intensity has been normalized by number of scans).

#FIGS. 3A-3H illustrate measured NMR spectra for one pulse (left column) and SUCCESS (right column) experiments targeting threonine performed on solutions of myo-inositol, threonine, and two mixtures (intensity normalized by number of scans).

#The patent and scientific literature referred to herein establishes knowledge that is available to those of skill in the art. The issued U.S. patents, allowed applications, published foreign applications, and references that are cited herein are hereby incorporated by reference to the same extent as if each was specifically and individually indicated to be incorporated by reference.

#As used herein, the recitation of a numerical range for a variable is intended to convey that the invention may be practiced with the variable equal to any of the values within that range. Thus, for a variable which is inherently discrete, the variable can be equal to any integer value within the numerical range, including the end-points of the range. Similarly, for a variable which is inherently continuous, the variable can be equal to any real value within the numerical range, including the end-points of the range. As an example, and without limitation, a variable which is described as having values between 0 and 2 can take the values 0, 1 or 2 if the variable is inherently discrete, and can take the values 0.0, 0.1, 0.01, 0.001, or any other real values≧0 and ≦2 if the variable is inherently continuous.

#In the present application, reference to an element in the singular is not intended to mean “one and only one” unless specifically so stated, but rather “one or more.” All structural and functional equivalents to the elements of the various embodiments described throughout this disclosure, known or later come to be known to those of ordinary skill in the art, are expressly incorporated herein by reference.